Biomedical Engineering Reference
In-Depth Information
seven principles. It also uses a tabular format (matrix) for laying out the test
requirements based on the various factors discussed earlier. The matrix con-
sists of two tables. See
Table 2.1
—Initial Evaluation Tests for Consideration
and
Table 2.2
—Supplementary Evaluation Tests for Consideration.
Table 2.3
is a biocompatibility flow chart for the selection of toxicity tests for 510(k)
s. It may be applicable to some Pharmaceutical Manufacturers Associations
(PMAs) also but not all PMAs. In addition, the FDA is in the process of pre-
paring toxicology profiles for specific devices. These profiles will assist in
determining appropriate toxicology tests for these devices. To harmonize
biological response testing with the requirements of other countries, the
FDA will apply the ISO standard, Part 1, in the review process in lieu of the
Tripartite Biocompatibility Guidance. The FDA notes that the ISO standard
acknowledges certain kinds of discrepancies. It states: “due to diversity of
medical devices, it is recognized that not all tests identified in a category will
be necessary and practical for any given device. It is indispensable for testing
that each device shall be considered on its own mertis: additional tests not
indicated in the table may be necessary.” In keeping with this inherent flex-
ibility of the ISO standard, the FDA has made several modifications to the
testing required by ISO 10993, Part 1. These modifications are required for
the category of surface devices permanently contacting mucosal membranes
(e.g., Intra Uterine Device (IUDs)). The ISO standard would not require acute,
subchronic, and chronic toxicity and implantation tests. Also, for externally
communicating devices with prolonged and permanent contact with tissue,
bone, or dentin (e.g., filling materials and dental cements), the ISO standard
does not require irritation, systemic toxicity, and acute, subchronic, and
chronic toxicity tests. Therefore, the FDA has included these types of tests
in the matrix. Although several tests were added to the matrix, reviewers
should note that some tests are commonly requested, while other tests are to
be considered and only asked for on a case-by-case basis. Thus, the modified
matrix is only a framework for the selection of tests and not a checklist of
every required test.
Reviewers should avoid a proscriptive interpretation of the matrix. If
a reviewer is uncertain about the applicability of a specific type of test for
a specific device, the reviewer should consult toxicologists in the Office of
Device Evaluation (ODE). The FDA expects that manufacturers will consider
performing the additional tests for certain categories of devices suggested
in the FDA-modified matrix. This does not mean that all the tests suggested
in the modified matrix are essential and relevant for all devices. In addition,
device manufacturers are advised to consider tests to detect chemical com-
ponents of device materials which may be pyrogenic. ISO 10993, Part 1, and
the appropriate consideration of additional tests suggested by knowledge-
able individuals will generate adequate biological data to meet the FDA's
requirements. Reviewers in the ODE will accept data developed according to
ISO-10993, Part 1, with the FDA-modified matrix as modified. Manufacturers
are advised to initiate discussions with the appropriate review division in
